Effects of cyclo- and lipoxygenase inhibitors on hypoxic vasoconstriction in isolated ferret lungs

J. E. Gottlieb, M. McGeady, N. F. Adkinson, J. T. Sylvester

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8 Scopus citations


To evaluate the role of leukotrienes in hypoxic pulmonary vasoconstriction, we measured steady-state pressor responses to graded hypoxia in isolated ferret lungs perfused with autologous blood containing 0.001, 0.03, 1, or 3 mM nordihydroguaiaretic acid (NDGA), 1 mM BW 755C, or 0.02-0.05 mM indomethacin. Untreated lungs served as controls. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F(1α), measured by radioimmunoassay, were markedly reduced in all treated lungs, indicating inhibition of cyclooxygenase. The maximum pressor response to hypoxia measured at a blood flow of 50 ml·min-1·kg-1 averaged 26.6 ± 2.4 Torr in untreated lungs and was not affected by BW 755C or 0.001-0.03 mM NDGA. Because BW 755C and NDGA inhibited cyclooxygenase at concentrations that did not affect hypoxic vasoconstriction and because both agents are thought to inhibit lipoxygenase with a potency greater than or equal to that with which they inhibit cyclooxygenase, these results do not support the possibility that hypoxic pulmonary vasoconstriction was mediated by leukotrienes. At concentrations of 1 and 3 mM, NDGA inhibited the maximum hypoxic pressor response by 57 and 95%, respectively. The mechanism of this attenuation is unknown; however, it was apparently not due to cyclooxygenase inhibition, since indomethacin enhanced the maximum hypoxic pressor response by 45%. Nor was it due to blockade of calcium entry or interference with the contractile process in pulmonary vascular smooth muscle, since 1 mM NDGA did not inhibit vasoconstrictor responses to KCl or prostaglandin F(2α).

Original languageEnglish (US)
Pages (from-to)936-943
Number of pages8
JournalJournal of applied physiology
Issue number3
StatePublished - 1988

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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